LncRNA CCAT1/miR-490-3p/VDAC1 Axis Promotes Colorectal Cancer Progression by Activating Glycolysis

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Colorectal cancer (CRC) progression is complex, involving genetic and epigenetic alterations.
• Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators in cancer development.
• Understanding the molecular mechanisms driving CRC is crucial for developing effective therapies.

Purpose of the Study:

• To elucidate the molecular mechanism of lncRNA CCAT1 in promoting colorectal cancer (CRC) progression.
• To investigate the roles of miR-490-3p and Voltage-Dependent Anion Channel 1 (VDAC1) in CCAT1-mediated CRC.
• To determine if the CCAT1/miR-490-3p/VDAC1 axis influences glycolysis in CRC.

Main Methods:

• Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess gene expression in CRC cell lines and normal cells.
• Dual-luciferase reporter assays to confirm interactions between CCAT1, miR-490-3p, and VDAC1.
• In vitro cell proliferation, glucose consumption, ATP production, and lactate secretion assays.
• In vivo xenograft mouse models to evaluate tumor growth and molecular changes.

Main Results:

• LncRNA CCAT1 was significantly upregulated in CRC cells and promoted proliferation and glycolysis.
• CCAT1 acted as a competing endogenous RNA for miR-490-3p, leading to VDAC1 upregulation.
• Overexpressing miR-490-3p or silencing VDAC1 inhibited CRC cell proliferation and glycolysis.
• In vivo, CCAT1 or VDAC1 knockdown reduced tumor growth and altered glycolysis-related gene/protein expression.

Conclusions:

• LncRNA CCAT1 promotes CRC progression by sponging miR-490-3p, upregulating VDAC1, and activating glycolysis.
• The CCAT1/miR-490-3p/VDAC1 axis represents a novel molecular mechanism in CRC pathogenesis.
• This axis holds potential as a diagnostic biomarker and therapeutic target for colorectal cancer.